Homozygous truncating PTPRF mutation causes athelia.

Abstract

Athelia is a very rare entity that is defined by the absence of the nipple-areola complex. It can affect either sex and is mostly part of syndromes including other congenital or ectodermal anomalies, such as limb-mammary syndrome, scalp-ear-nipple syndrome, or ectodermal dysplasias. Here, we report on three children from two branches of an extended consanguineous Israeli Arab family, a girl and two boys, who presented with a spectrum of nipple anomalies ranging from unilateral hypothelia to bilateral athelia but no other consistently associated anomalies except a characteristic eyebrow shape. Using homozygosity mapping after single nucleotide polymorphism (SNP) array genotyping and candidate gene sequencing we identified a homozygous frameshift mutation in PTPRF as the likely cause of nipple anomalies in this family. PTPRF encodes a receptor-type protein phosphatase that localizes to adherens junctions and may be involved in the regulation of epithelial cell-cell contacts, peptide growth factor signaling, and the canonical Wnt pathway. Together with previous reports on female mutant Ptprf mice, which have a lactation defect, and disruption of one allele of PTPRF by a balanced translocation in a woman with amastia, our results indicate a key role for PTPRF in the development of the nipple-areola region.

• Authors: Guntram Borck, Liat de Vries, Hsin-Jung Wu, Pola Smirin-Yosef, Gudrun Nürnberg, Irina Lagovsky, Luis Henrique Ishida, Patrick Thierry, Dagmar Wieczorek, Peter Nürnberg, John Foley, Christian Kubisch, Lina Basel-Vanagaite
• Journal: Human genetics (Hum Genet) Vol. 133 Issue 8 Pg. 1041-7 (Aug 2014) ISSN: 1432-1203 [Electronic] Germany
• PMID: 24781087 (Publication Type: Journal Article)

Chemical References

• PTPRF protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 2

Topics

• Adolescent
• Adult
• Animals
• Breast (abnormalities, pathology)
• Breast Diseases
• Cells, Cultured
• Child
• Child, Preschool
• Congenital Abnormalities (etiology, pathology)
• Female
• Fibroblasts (metabolism, pathology)
• Frameshift Mutation (genetics)
• Gene Expression Profiling
• Genome-Wide Association Study
• Homozygote
• Humans
• Infant
• Male
• Mice
• Nipples (metabolism, pathology)
• Pedigree
• Polymorphism, Single Nucleotide (genetics)
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (genetics)